Understanding Androgenetic Alopecia

[paleocapa89]

This is a really informative thread, although it crushes my hope of curing this disease in the sort term

I would like to ask a question though that I didn't really find answer yet. If a person regrew some of his hear with a treatment like finasteride or something, why does he experience accelerated hairloss after dropping the treatment? If he regrew his hairs due to the cells repair mechanism, I would think that he will lose those hairs again in the same time he initially lost them.

 

[Swoop]

This is a really informative thread, although it crushes my hope of curing this disease in the sort term

I would like to ask a question though that I didn't really find answer yet. If a person regrew some of his hear with a treatment like finasteride or something, why does he experience accelerated hairloss after dropping the treatment? If he regrew his hairs due to the cells repair mechanism, I would think that he will lose those hairs again in the same time he initially lost them.

Hehe it's a hypothesis. But it's based around research from other researchers/papers. Don't worry perhaps it's something else, who the hell knows man. Although at this point I do think Androgenetic Alopecia is simply extremely hard to reverse, and I find senescence the most logical thing to assume based on current research. I have made a article about this recently; http://hairandscience.com/possible-...r-cell-cycle-arrest-in-androgenetic-alopecia/ (its educational only, no donations or ads whatsoever)

I'll try to explain it in a more logical manner though (scroll down if you want to have answer on your question lol). First if we look at the observations in Androgenetic Alopecia we see the following which is known or shown in various papers;

- Hair follicle miniaturization which is characterized by progressive thinning of the hair

- Generally in early Androgenetic Alopecia no inflammation is seen, later micro-inflammation can be seen sometimes around the hair follicle. In late stage Androgenetic Alopecia we see that even fibrosis can show up and even destroy (parts) of the hair follicle.

- The inflammatory infiltrate that is seen is mainly composed of lymphocytes and histiocytes and also a increase of mast cells is seen. I quote;

The inflammatory infiltrate was composed mainly of lymphocytes and histiocytes. It was more concentrated around the upper portion of the follicles (around the lower portion of the infundibulum and isthmus). These
findings correlate with previous reports.9,16,18

In early (mild and moderate) Androgenetic Alopecia, mononuclear cellular inflammatory infiltrate, composed predominantly of lymphocytes and mononuclear cells, was distributed within the adventitial sheath. The mast cells were increased in number and showed degranulation which became marked in advanced Androgenetic Alopecia, leaving mast cells with few or even no intact granules

Perhaps it's interesting to know that large amounts of PGD2 are actually found in mast cells (degranulation). Thus that could be one logical explanation of increased PGD2 levels in the balding scalp. Hmm.. Cotsarelis didn't mention that.. Oh well.

- Generally we see that Androgenetic Alopecia is extremely hard to reverse. Some lucky individuals manage to get great results going with hitting the androgen/AR angle hard but the overwhelming majority not.

- 17b-estradiol seems to help sometimes with reversing Androgenetic Alopecia in combination with hitting the androgen/AR angle.

- AR has been shown to be hugely involved on a genetic level

Now off to some other things that have been shown;

- The lack of progenitor cells in balding scalp, however this is most likely a secondary event as there is a decrease of dermal papilla cells when the hair follicle miniaturizes. The dermal papilla is a instructive niche for the progenitors. The progenitors are depended on the DP cells. This has been shown in various papers, just recently also at the hair congress in a paper.

-A decrease in DP amount leads to hair follicle miniaturization. Bigger amount of DP in the hair follicle leads to a bigger hair follicle. Also has been shown that if you below a certain threshold of DP cells, anagen initiation can't occur either.

If you have read the article furthermore you can either see that senescence is pointed out or simply factors that are highly implicated in senescence. Or "stress" that can lead to senescence (DNA damage, ROS etc).

Now if you go to the classical senescence model;

It kinda correlates also. Think of these cells like your dermal papilla niche. A hair follicle has around 500 dermal papilla cells.

Step 1: Damage and developmental cues

This would be where Androgenetic Alopecia starts. We know that it's androgen and AR dependent. I have no clue why the hell this "stress" happens though. Could be DNA damage or ROS or something else or something else. We do know that the AR plays a huge role based on genetic studies.

Step 2: Senescence

Some of your DP cells can't handle the stress anymore and start to transform into a senescent state. Cells can show gradual increase in "senescent state" too. Pre-senescent, senescent and late senescent as you can see

here; http://www.nature.com/nature/journal/v509/n7501/images_article/nature13193-f3.jpg

Step 3: SASP

Because of this eventually they will start to secrete inflammatory factors which is a hallmark of senescence called SASP. So because of some senescent DP cells now inflammation kicks in. I believe the inflammatory factors secreted by the DP cells cause apoptosis too of neighboring DP cells.

Step 4: Recruitment.

I quote;

"A unified model Based on the above-discussed evidence, we propose that senescence is a key component of tissue remodelling both in normal development and physiology, and in multiple pathologies. We also propose that, in general, cellular senescence coordinates tissue remodelling through three sequential processes: first, a stable proliferative arrest; second, a secretory phenotype (SASP) that recruits immune cells, notably including T helper lymphocytes and macrophages; and, third, the mobilization of nearby progenitor cells that repopulate the tissue (FIG. 3)."

Jup indeed. This is seen in Androgenetic Alopecia too. And the hair follicle obviously remodels heavily during Androgenetic Alopecia, the whole morphology changes.

In this step you would assume that normally repair should happen. But this doesn't happen obviously. Because the hair follicle is under constant stress from the AR.

Step 5 and 6: Clearance and regeneration

Well forget this step. Doesn't happen automatically in Androgenetic Alopecia. If you are on time however you might repair some of the damage, like we see with finasteride. Some dermal papilla cells might be still in a pre-senescent or early senescent state. So when you remove the "stress" you might actually get some benefit if you are lucky. Prevention is best though obviously.

Step 7: Doom phase

If you don't do anything you will be eventually left with a miniaturized hair follicle that is just doomed. Fibrosis can even set in that might lead to destruction of the hair follicle (horrible). The whole morphology has changed meanwhile. Yeah done case pretty much.

Anyway this is very superficial. To put it simply it's all about damage and stress over time. Here is a good video that I recommend you to watch that relates to all of this and how future strategies might be applied to such problems;

[video=youtube;tXjv2PfRJ3s]https://www.youtube.com/watch?v=tXjv2PfRJ3s[/video]

Remember though this is all a hypothesis. Perhaps it's something different who the hell knows.






Now about your question;

http://www.regrowshair.com/wp-content/uploads/2006/11/mean_change_crossover_data_chart.gif

We see that when you go on finasteride for 1 year and you stop taking it it takes 1 year to go back to a little below baseline. Thus we can say that all the hair you have gained in one year will be lost in 1 year, although anecdotal experience might say otherwise. Right?

That being said some nuances might not be explainable by senescence what we see in Androgenetic Alopecia, but then again we have much to learn in terms of senescence and Androgenetic Alopecia too obviously.

 

[Armando Jose]

Good work Swoop,
but you write "This would be where Androgenetic Alopecia starts. We know that it's androgen and AR dependent. I have no clue why the hell this "stress" happens though. Could be DNA damage or ROS or something else or something else"

it is possible that problmes with sebum or sebum flow (Ex. rancidity) can have a role in the first events of the multifactorial problem of common hairloss?

 

[Swoop]

Good work Swoop,
but you write "This would be where Androgenetic Alopecia starts. We know that it's androgen and AR dependent. I have no clue why the hell this "stress" happens though. Could be DNA damage or ROS or something else or something else"

it is possible that problmes with sebum or sebum flow (Ex. rancidity) can have a role in the first events of the multifactorial problem of common hairloss?

Armando ,

I do think the sebaceous gland has a role in Androgenetic Alopecia. But I personally don't believe it is one of the first events. To me that would be clearly the transformation of DP into a altered cell cycle state which leads to proliferation arrest and dysfunction. I believe the problem originates from within the DP when the AR is activated.

 

[Armando Jose]

Armando ,

I do think the sebaceous gland has a role in Androgenetic Alopecia. But I personally don't believe it is one of the first events. To me that would be clearly the transformation of DP into a altered cell cycle state which leads to proliferation arrest and dysfunction. I believe the problem originates from within the DP when the AR is activated.

Thanks Swoop for your response.

Because of the miniaturization process that exists in hair loss before it, I think the initial problem is that stem cells do not come to DP sufficient. And in this case solidification of sebum may have an important role. This is my idea.

 

[Swoop]

Thanks Swoop for your response.

Because of the miniaturization process that exists in hair loss before it, I think the initial problem is that stem cells do not come to DP sufficient. And in this case solidification of sebum may have an important role. This is my idea.

Have you read this study? http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0625.2007.00666.x/pdf

Jahoda is very smart and methodical. That study was pretty much the first one to look at it really from an observation level how the cells move and how the morphology changes of a miniaturized hair follicle and a healthy hair follicle through cycles. He also hypothesizes 3 scenarios that could contribute to the DP decrease seen in Androgenetic Alopecia. You can look at the longitudinal section in that study and see how a hair follicle proceeds in the miniaturization process;

Remember that is a pretty old study but very impressive nonetheless.

You might be right though, although I personally don't concur with the sebum part you mention. It's possible that there is a problem for instance with the re-population of DP. I would believe then this would be somewhere from the mesenchyme. Actually even now it is hypothesized that DP repopulate to some extent from outside the DP niche at early anagen when transitioning from telogen. The details are not known yet. It could be for instance that the dermal sheath repopulates the DP to some extent as shown recently in a rodent model. After all that is kinda the hypothesis of Replicel too.

If there was a re-population problem I would argue that Androgenetic Alopecia wouldn't proceed so fast in certain individuals though. So I believe the DP cells get damaged/stressed and the sh*t starts there.

Can you elaborate more on your own view? How did you come to that? What is your thought process?

 

[Armando Jose]

thank you very much for the study, please permit me a few days to read it carefully and be able to comment. I like Jahoda studies.


I have many years mulling over common baldness and comments from Bryan Shelton became convinced that if hormones are involved, it is not what defines a person to stay bald and some not. Androgens on hair on the head are present many years before puberty, because the hair to grow needs an operating sebaceous gland, which produces its own hormones from cholesterol.
Moreover I indicated that sebum is necessary but unstable and must be generated continuously and eliminating at the same time or being spent. If it accumulates problems begin, chemical changes, physically and biologically. I also believe that there is a transport of sebum into the hair reaching the dermal papilla and entering the same hair fiber.

 

[paleocapa89]

Probably noone has ever done such an experiment, but what happens if you give testosterone to a child who has male pattern baldness genes? Will he start balding at a young age? Also, how can a trans woman grow her hair out? Can estrogen wake up the senescent cells? I'd also be curious about a trans woman's prostaglandin levels in her scalp where she is regrowing.

(sorry for my layman science)

 

[amberjack]

what do you do for living (job) swoop, and what do you think of psi..i have psi from the group buy but didnt started yet..planing soon..

 

[Armando Jose]

Probably noone has ever done such an experiment, but what happens if you give testosterone to a child who has male pattern baldness genes? Will he start balding at a young age? Also, how can a trans woman grow her hair out? Can estrogen wake up the senescent cells? I'd also be curious about a trans woman's prostaglandin levels in her scalp where she is regrowing.

(sorry for my layman science)

It is not advisable use hormones in prepubertal childrens
http://www.ncbi.nlm.nih.gov/pubmed/23426834

 

[paleocapa89]

It is not advisable use hormones in prepubertal childrens
http://www.ncbi.nlm.nih.gov/pubmed/23426834

Yes I am very aware of that I was wondering theoretically. As the study shows sometimes it happens, I once read that somewhere that certain tumors can excrete hormones so I'd assume it can also happen endogenously as well. I was also wondering about the study when castrated people were given testosterone and they started balding rapidly? How is that possible? I thought that it takes years of androgen exposure to start balding.

 

[Firemythos]

Did anyone heard of that sexual hormone binding globulin short SHGB?

Let me quote from wikipedia:
"
Thus, bioavailability of sex hormones is influenced by the level of SHBG. The relative binding affinity of various sex steroids for SHBG is dihydrotestosterone (DHT) > testosterone > androstenediol > estradiol > estrone."

Actually SHBG is binding DHT and does it most effectively.
Maybe some balding men are starting balding way earlier than they normally would because of low SHBG-levels. High SHBG means low DHT-activity.
They are a few things which are increasing SHBG like green tea extract.

This sounds like a reall good way for alternative medication. Instead of artificial 5AR-Inhibtors you start to increase SHBG which will decrease your DHT.


Thoughts?

 

[Swoop]

I have many years mulling over common baldness and comments from Bryan Shelton became convinced that if hormones are involved, it is not what defines a person to stay bald and some not. Androgens on hair on the head are present many years before puberty, because the hair to grow needs an operating sebaceous gland, which produces its own hormones from cholesterol.
Moreover I indicated that sebum is necessary but unstable and must be generated continuously and eliminating at the same time or being spent. If it accumulates problems begin, chemical changes, physically and biologically. I also believe that there is a transport of sebum into the hair reaching the dermal papilla and entering the same hair fiber.

Thanks. Does sebum flow downwards too then? Or only upwards? What do the studies say about that? And what do you exactly mean by "became convinced that if hormones are involved, it is not what defines a person to stay bald and some not"? Genetics eventually determine that right Armando? Or do you think otherwise?

what do you do for living (job) swoop, and what do you think of psi..i have psi from the group buy but didnt started yet..planing soon..

Doing a second study now in bio science. Working as a hospitality employee and I am since recently also lecturing high school kids. Still living the student life.

Anecdotal evidence seems to say that PSI works. But... I still have problems with the clinical trial done. The 14 day trial showed like what 5% of hair growth? Well that's not much. But then they ran this clinical trial; https://clinicaltrials.gov/ct2/show/NCT00418730 for 16 weeks applying a 2% PSI solution TWICE daily vs placebo and a minoxidil group. That is more than 4 gram of PSI over the time period of 16 weeks.

So ask yourself the question; would any company really drop the treatment if it worked that great? What do you think?

If the people trailing PSI don't get results this time it's a closed chapter in my opinion. Can't go on forever right... Good luck and keep us updated if you can!

Yes I am very aware of that I was wondering theoretically. As the study shows sometimes it happens, I once read that somewhere that certain tumors can excrete hormones so I'd assume it can also happen endogenously as well. I was also wondering about the study when castrated people were given testosterone and they started balding rapidly? How is that possible? I thought that it takes years of androgen exposure to start balding.

Jup, if you would inject a kid with Androgenetic Alopecia genes with a good enough amount of testosterone he would start displaying Androgenetic Alopecia.

James B. Hamilton did most of that research. He observed and tested on eunuchoids and castrates. Back then many guys were castrated when they showed a mental disease (harsh). Anyway his findings and observations were;

1. People who were castrated pre-pubertally or eunuchoids displayed pretty much complete retention of their hair. These are people that didn't mature sexually. Even the slightest recession failed to disappear in this group at the frontal regions. Not only that, often they retained their temple points almost to the lateral edges of the eyebrows. Like this;

2. People who were castrated between 14 and 19 years of Androgenetic Alopecia showed no form of any baldness or very little recession. But this is logical because some of them already hit puberty in this time and even a very short amount of time of (surging or high) androgen expression can lead to recession. Especially to those hair follicles at the utmost edge of the hairline and temple points like you see in the picture here above. I think you know what I mean.

3. People who were castrated between the age of 20 to 43 years old showed variable degree of baldness. But this is completely logical obviously.

Now what he noticed that every time a person was castrated at any age balding would stop. It didn't reverse though.. Sometimes there was reversal to some extent though. But hey, we see sometimes some reversal with people on compounds that hit the androgen/AR angle too.

Now more importantly he actually tested on some of these eunuchoids and castrated men and started injecting them with testosterone over longer periods of time (a few years). Well you know the answer already. Some started balding, some didn’t. Their hairline would show recession or their crown went thinning. When he stopped injecting them the balding process stopped again though.


In terms of transsexuals it helps obviously that they demolish their androgen levels. Not only that they often use 17b-estradiol or bio-identical compounds. This is the primary female sex hormone.

Women have obviously way higher levels of 17b-estradiol and way less androgens in their body than men. However they also have more aromatase activity in their scalp (converts T to E). And less 5ar activity.. Basically their scalp is a heaven for estrogen to flourish. Interestingly when women start to suffer from PCOS for example (hormonal imbalance that causes more expression of androgens) some of them can already start displaying female pattern hair loss.

When men take 17b-estradiol or similar compounds with the same biological activity it can reverse their Androgenetic Alopecia to great extent with castration or compounds that pretty much induce castration. 17b-estradiol seems to be the god molecule for human scalp hair growth basically.

However even castration + 17b-estradiol can't always regrow hair in men...

Male and female scalp E2-stimulated hair follicles were analyzed by cDNA microarray. Of 1300 genes tested, more than 600 E2-responsive genes were detected in both experiments

There are some pathways induced by estrogen that probably work very good in reversing the damage or growing hair.. There are certainly interesting correlations to be made but ultimately it’s extremely complex as you can imagine.

 

[Mikazz]

Elevated estrogen level is actually a cause of hair loss in women, and too much estrogen is bad overall (linked to cancer in women and men). I'm pretty sure elevated estrogen level in men would actually increase, to some extent, the rate of hair loss. There is a lot of similitude between prostate cancer and hair loss. Both are caused by the oxidative stress induced by elevated DHT level. In men, High estrogen level increases prolactin via hyperprolactinemia, and higher prolactin level increases 5-alpha-reductase which causes more DHT, and more oxidative stress in the dermal papilla and in the prostate cells. In women, this same pathway is suspected to cause breast cancer (at least, we know for sure that elevated estrogen is linked to breast cancer, most probably via prolactin).

Women defends themselves against hair loss by other mechanisms. The one mechanism I find interesting is the protective effect of the progesterone hormone, the master anti-dht. Depending on where womens are in their cycle, whey will experience different levels of progesterone and when progesterone level is high, they experience better hair quality.

Interestingly, progesterone lotion has been tested on men, and it's like a weaker (and safer) finasteride, it helps to slow down or stop hair loss and even regrowth hairs in some case. In fact, finasteride is considered a progestin, a synthetic form of progesterone. When finasteride is combined with a 5-alpha reductase it becomes a dihydro-finasteride while a progesterone will become a dihydro-progesterone.

 

[Swoop]

Did anyone heard of that sexual hormone binding globulin short SHGB?

Let me quote from wikipedia:
"
Thus, bioavailability of sex hormones is influenced by the level of SHBG. The relative binding affinity of various sex steroids for SHBG is dihydrotestosterone (DHT) > testosterone > androstenediol > estradiol > estrone."

Actually SHBG is binding DHT and does it most effectively.
Maybe some balding men are starting balding way earlier than they normally would because of low SHBG-levels. High SHBG means low DHT-activity.
They are a few things which are increasing SHBG like green tea extract.

This sounds like a reall good way for alternative medication. Instead of artificial 5AR-Inhibtors you start to increase SHBG which will decrease your DHT.


Thoughts?

Good point. Look at my blood test taken 2 years ago or something;

See the SHBG? Totally out of reference range. Pretty low. There is a huge correlation made between low SHBG and aggressive balding people in studies (NW3+ before the age of 30). Look at my free testosterone. That is pretty high. Like you mention SHBG levels are decreased by androgens and increase with estrogens. Lower SHBG causes higher bio-available androgens.

Elevated estrogen level is actually a cause of hair loss in women, and too much estrogen is bad overall (linked to cancer in women and men). I'm pretty sure elevated estrogen level in men would actually increase, to some extent, the rate of hair loss. There is a lot of similitude between prostate cancer and hair loss. Both are caused by the oxidative stress induced by elevated DHT level. In men, High estrogen level increases prolactin via hyperprolactinemia, and higher prolactin level increases 5-alpha-reductase which causes more DHT, and more oxidative stress in the dermal papilla and in the prostate cells. In women, this same pathway is suspected to cause breast cancer (at least, we know for sure that elevated estrogen is linked to breast cancer, most probably via prolactin).

Women defends themselves against hair loss by other mechanisms. The one mechanism I find interesting is the protective effect of the progesterone hormone, the master anti-dht. Depending on where womens are in their cycle, whey will experience different levels of progesterone and when progesterone level is high, they experience better hair quality.

Interestingly, progesterone lotion has been tested on men, and it's like a weaker (and safer) finasteride, it helps to slow down or stop hair loss and even regrowth hairs in some case. In fact, finasteride is considered a progestin, a synthetic form of progesterone. When finasteride is combined with a 5-alpha reductase it becomes a dihydro-finasteride while a progesterone will become a dihydro-progesterone.

Nice thank you. Yes indeed. To much of estrogen can cause problems too in women. However in men? Never really saw that. Never did I see case or anecdotal reports of hair falling out in combination with anti-androgen therapy. It's always cessation of hair loss with either no hair growth or hair growth to some extent which can be even major.

When you look at the cDNA microarray of E2 stimulated hair follicles you also see differences between male and scalp human hair follicles in terms of gene expression. http://elib.tiho-hannover.de/dissertations/conradf_ss04.pdf.

The molecular mechanisms of estrogen action are relatively well investigated, but only a few target genes with consensus ERE (primary-responsive genes) are known so far, such as progesterone receptor, prolactin, lactoferrin, ovalbumin, vitellogenin, cathepsin D1, pS2, glucose-6-phosphate dehydrogenase, c-fos, c-jun, c-myc and choline acetyltransferase. There are more genes activated eventually by estrogen but without apparent ERE: EGF, EGFR, cyclin D1 and others, which can be termed the secondary E2-responsive genes

Another study; http://press.endocrine.org/doi/full/10.1210/er.2006-0020

Just a few important genes regulated by ERs, which also are recognized for their involvement in hair growth control, are listed here as examples: progesterone receptor, EGFR, several growth factors like IGF-I, TGF-α and TGF-β, cathepsin D, and several protooncogenes (e.g., c-fos, c-myc, and c-jun), as well as an array of heat shock proteins. WNT, BMP's, Cyclin D1, Homeobox proteins etc etc...

You say the magic word also. Estrogen is a carcinogen, it is even classified like that (group 1 carcinogen); http://www.cancer.org/cancer/cancer...cinogens/known-and-probable-human-carcinogens

For example, estrogen is a known carcinogen that occurs naturally in the body.

And to no surprise if you even look at the fraction of the pathways implicated in relation to estrogen and hair follicle growth/cycling you will know immediately why it is considered a carcinogen.

Estrogen can also modulate factors like P53, P21 etc (just look at breast cancer what you mention). These are major regulatory master pathways implicated in cell cycle decisions/cell cycle progression and also senescence/cell cycle arrest. Senescence is generally seen as irreversible however in animal models it has been shown to be reversible sometimes. I guess it's time dependent too because cells can sow gradual forms of senescence.

Ultimately we still have a lot to learn in relation to everything. As you can imagine though the likelihood of a drug coming out that will grow hair well in Androgenetic Alopecia is extremely low to non-existent in my opinion. At least in the classical form of a drug acting selectively upon a pathway, but even drugs with a more broad biological activity. There is another problem also. The pharmaceutical industry will never ever even begin to explore some (direct) modulation of some pathways simply because that is way too dangerous ESPECIALLY for something like Androgenetic Alopecia which is seen as a cosmetic problem. A classical example of this is the stoppage of the HH agonist of Curis for hair growth. It was stopped because of safety issues immediately.

Regenerative therapy/gene therapy is 100x more likely to provide us an answer in the future in my opinion.

 

[Baldybald1]

Swoop, I wish I could give you a laboratory and fund you to get the cure because you have a lot of knowledge. And I would ask you to keep things secret same as cots and shisheido )

 

[Mikazz]

[FONT=ms sans serif, arial, helvetica, sans-serif]-> "Insulin resistance, even without obesity, results in lower SHBG levels. This is associated with increased intra-abdominal fat deposition and an unfavorable cardiovascular risk profile."[/FONT]
[FONT=ms sans serif, arial, helvetica, sans-serif]Men with early onset of baldness have also been shown to be in a pre-diabetics state. Looks like insulin resistance might be causing low SHBG.
They also have lower testosterone level (lower testosterone is a symptom of more dht, and higher testorone is less dht).
IMO, early onset of hair loss is very related to unhealthy lifestyle, insulin resistance do not happens without a reason. If you drink multiple can of coca cola everyday , watch out for multiple health problems such a early onset of hair loss (if susceptible) and type 2 diabetes.

[/FONT]

As you can imagine though the likelihood of a drug coming out that will grow hair well in Androgenetic Alopecia is extremely low to non-existent in my opinion.

[FONT=ms sans serif, arial, helvetica, sans-serif]I also think that finasteride/dutasteride is already near the summum of what we will be ever able to do with a single drug. It decimate the testosterone to dht pathway for days in the dermal papilla for almost everyone, nothing will ever be as powerful.

[/FONT]

 

[persistentone]

Regenerative therapy/gene therapy is 100x more likely to provide us an answer in the future in my opinion.

I have always thought a good approach would be to clone a person's hair follicles, grow those under laboratory conditions, and then transplant. What are alternate approaches using regenerative/gene therapy? How far away do you think those are?

Thanks for posting your SHBG and free testosterone numbers. That was interesting to compare against my own. FYI: a better marker for free testosterone is what is known as "free and weakly bound testosterone". This uses a more accurate chemistry and includes the fraction bound to albumin, which is actually bioavailable. This type is known as "bioavailable testosterone" as well. "Free testosterone can underestimate the actual amount significantly.

 

[Firemythos]

Are there studies or information on how to increase SHBG?

I read somewhere that a study showed that SHBG is metabolised in the liver and it is good health indicator for the liver.

 

[abcdefg]

Yeah its kind of funny the stuff James B. Hamilton did that long ago is still to this day the only proven way we know of for sure to actually stop male pattern baldness.
Swoop you use RU and finasteride then right. What do you think of the safety long term of these 5-ar inhibitors? I get a little worried it inhibits 5-ar 3 , crosses blood brain barrier, and might affect neurotransmitters. That is my biggest worry along with any possible prostate cancer effect. Mainly why I have never tried it, and my male pattern baldness is very very slow so im not in dire straights.
Your opinion I guess is use an AA right away.